This application proposes a laboratory study designed to test the association between two trait markers for alcohol use disorders (i.e., cue elicited craving and acute responses to alcohol) and two candidate polymorphisms linked to these trait markers (i.e., DRD4 VNTR and GABA Pro385/Ser SNP). Specifically, this proposal will: (1) test the relationship between the DRD4 VNTR polymorphism and cue elicited craving for alcohol; (2) investigate personality factors that may mediate the relationship between craving for alcohol and the DRD4 candidate gene; and (3) test the association between the GABA Pro385/Ser SNP and one's sensitivity to the effects of alcohol. We will compare 40 individuals with the DRD4 VNTR risk allele against 40 individuals without it in an alcohol challenge paradigm. Likewise, our matched research design will include 40 individuals with GABA risk Pro/Ser substitution and 40 individuals without it. We expect individuals with the risk alleles to score higher on measures of craving for alcohol (DRD4 VNTR) and lower on measures of sensitivity to the acute physiological and subjective effects of alcohol (GABA Pro/Ser SNP). The long term objective of this proposal is to advance our understanding of the genetic, biological, and behavioral determinants of alcohol addiction by utilizing a highly controlled laboratory design to test preliminary genetic findings.